1. Field of the Invention
The current invention is referred to vaccine compositions for subcutaneous administration containing gangliosides useful for the immunological treatment of autoimmune diseases, infectious diseases and tumors, without any additional adjuvant.
2. Background of the Prior Art
For a long time it is known the intention of using as immunological treatment of autoimmune diseases and cancer, for instance the U.S. Pat. No. 4,965,198 patent describes the use of ganglioside GM2 in the prevention and therapy of such diseases. In the filed patent EP-A-661061 and in the U.S. Pat. No. 6,149,921, vaccine compositions are described in order to stimulate or increase the antibody response against a ganglioside which consists in an immunogen and an immunological adjuvant.
The described immunogens are: VSSP (very small size proteoliposomes) constituted by the association of N-AcetylGM3 and N-GlycolylGM3 gangliosides from now on: (N-AcGM3) and (N-GcGM3), with the outer membrane protein complex (OMP) from Neisseria meningitidis. 
Such immunogens from now on will be denominated N-AcGM3/VSSP and N-GcGM3/VSSP; they are very small size and practically invisible to the Electronic Microscope, water soluble and with increased floating capacity.
For the vaccine compositions described in EP-A-661061 and U.S. Pat. No. 6,149,921 the utilization of an adjuvant, such as the very well known Freund incomplete adjuvant, was required.
In the filed patent WO-A-02145746 vaccine compositions are described containing (A) one or more antigens with low immunogenicity; (B) VSSP with incorporated gangliosides mainly N-AcGM3/VSSP and N-GcGM3/VSSP; and (C) eventually one or more adjuvants.
In the paper of Carr A. et al., published in Melanoma Research, 2001, Vol. 11, pp 219-227, the anti-tumor activity of a vaccine containing N-AcGM3 ganglioside in mice bearing melanoma B16 is described.
In that article the influence of the presence of an immunological adjuvant, especially the complete Freund's adjuvant or the incomplete Freund's like adjuvant Montanide ISA 51, is also studied. The vaccines were administered intramuscularly and the emerging conclusion is that mice immunized with N-AcGM3/VSSP, with any of the adjuvants, Freund or Montanide ISA 51, showed IgM and IgG anti-N-AcGM3 responses at week 8th (Table 1). In contrast, the N-AcGM3/VSSP vaccine without any adjuvant did not show any immunogenic response (page 223, right column).
Therefore, the state of the art teaches that vaccines containing VSSP conjugated with gangliosides should be formulated with adjuvants, mainly the Freund's (complete or incomplete) or Montanide ISA 51.
However, it is very well known that when they are parentherally administered, such adjuvants, particularly the Freund's complete adjuvant, provoke some inconvenient side effects such as chronic inflammation in the injection site, eventual granulomas and sterile abscess or ulcerative necrosis in tissues. Montanide ISA 51 is less aggressive but also can cause some inflammatory disorders.
It would be very desirable from the point of view of their applications in the immunological treatments of autoimmune, infectious and tumoral diseases to have new gangliosides vaccine compositions which are less aggressive in the injection site and that could be more easily used with less inconvenient for the patients.
The authors of the present invention have discovered that the ganglioside based vaccines formulated with VSSP, when administered subcutaneously can be used without any adjuvants while there still be present the relevant immunological properties.
The aims of the present invention are new vaccine compositions included in VSSP, preferably N-AcGM3/VSSP and N-GcGM3/VSSP, which do not contain any immunological adjuvant and are administered subcutaneously.
Is also an objective of the present invention a method for the treatment of a patient who required a reinforcement of their immunological response consisting in the subcutaneous administration of the ganglioside vaccine compositions, preferably N-AcGM3/VSSP and N-GcGM3/VSSP, which do not contain any immunological adjuvant.
Is also the objective of the present invention N-AcGM3/VSSP and/or N-GcGM3/VSSP vaccine compositions not containing other antigenic components different from gangliosides or any other immunological adjuvants and are administered subcutaneously.